Prognosis

Topics Discussed in this section:

• Will my child outgrow this?
• How long does an exacerbation last?
• What is the Long-Term Outcome of this Illness?
• Will IVIG or Plasmaphoresus (plasma exchange, PEX) or Antibiotics help my child?
• What about Prophylactic Antibiotics – How long should my child stay on them?
• Treatment and Relapse (Survey Results by PANDAS Network.org)

The question that most parents have is whether their child will eventually “outgrow” PANDAS. One has to look at that question from two points of view, does a child “outgrow” getting strep infections (the trigger for PANDAS) as they hit adulthood and/or does the child “outgrow” the actual autoimmune disorder. There is currently no long-term prospective study on the outcome of this newly identified (1998) illness.

According to Swedo in her landmark paper, “The age of the host also may determine susceptibility (to PANDAS); it is known that rheumatic fever is quite rare after puberty. It appears that the developmental changes of adolescence may decrease the vulnerability to the cross-reactive autoimmunity. It is also possible that the postpubertal decrease in incidence (44) is related to the fact that the rate of GABHS infections falls dramatically around the age of 12, presumably because the child has developed antibodies against the conserved portion of the M-protein (i.e., the child is able to make antibodies that recognize all strains of GABHS) (V. Fischetti, personal communication, 1994).”

As for the autoimmune aspect of PANDAS, theories are that:

1) overtime the body develops a natural immunity through a natural immunological maturing process

2) the thymus (producer of antibodies in children) largely shuts down at adulthood.

The hope is that the child’s immune system will eventually learn to develop the correct antibody response to strep as they get older.

When discussing PANDAS, one has to remember that strep is the trigger. With PANDAS, it is important to keep strep at bay and not to incite the autoimmune response over and over. Hence, why many children stay on a prophylactic dose of antibiotics well into adulthood to try to prevent strep infections. Some other children do fine on periodic courses of antibiotics (just when a new exacerbation occurs). HOWEVER, the majority of the cases currently connected to this website have the more severe type of PANDAS that is highly reactive to strep or other illnesses like coughs, flu, fever or colds.  These children will maintain their hope for possible full recovery at puberty only with ongoing protection from antibiotics, IVIG or plasmaexchange or a combination of these.

Even if a subsequent exacerbation is caught quickly, it does not mean it will be an easier recovery or any less severe. We are hearing from anecdotal reports that often exacerbations worsen each time they occur.  There is no way in knowing how a child will react. The immune system is on high alert. No matter what your choice of treatment, protecting the child from more strep infections or proximity to ANYONE sick with strep in the First Year of Healing needs to remain high priority. We, as parents and doctors, owe it to these children to give them the best chance of recovery and no future suffering.

PANDAS may stop for some girls at onset of menses.  It is currently believed through follow up conversations with parents that only 2-3% of all pediatric cases have recurring issues into young adulthood. It is not clear yet if that 2-3% did not get adequate preventative care in the earlier years. Doctors will try to clarify that issue in the near future. The NIMH is completing a prospective 8-year study of PANDAS children in 2010 following children with PANDAS-onset OCD and Non-PANDAS OCD. According to Swedo in a February 2011 interview, she stated that half of the children in that 8 year study, no longer had symptoms. Some still had some type of symptoms present but they were able to be managed through medications or they were so minute, they did not impede the person’s life and no medication was even needed. It is not clear what type if any treatment these children will have received.

Whether PANDAS can eventually become a chronic condition that will continue into adulthood, no one really has an answer for that. Even practicing doctor and researcher, Dr. Tanya Murphy states in Clinical Factors Associated with PANDAS  (pdf provided by the NIH). “Whether children with a PANDAS subtype typically will go on to remission or progress to a more chronic course of illness is not known.”  For this reason, parents MUST remain vigilant in protecting their children from contracting strep. Also. do not assume one can forgo treatment as a child in hopes that puberty holds the key.

If a child receives antibiotics a typical 5 day or 10 day course of antibiotics with an exacerbation parents and doctors report that after a strep exposure (some children react microbially) or a strep infection – the episode lasts 5 to 6 weeks and then it gradually dies out. Low level anxiety and OCD/TIC issues may remain permanently or fade away after several weeks or months. There are times (cases #1 and #2) where the exacerbation takes 4 to 6 months to remit.

However, in many of the acute cases here the typical course of antibiotics is not helpful and the child continues to suffer for months and symptoms often increase in severity. We are not clear if our acute cases are the exception or “the rule” with PANDAS. The acute cases have clearly having an encephalitic reaction to strep and aggressive treatment needs to be considered.

 

It is still not entirely known.

Doctors watching PANDAS patients over the last decade feel that if the child continues to suffer from some dysfunction (mood lability or anxiety or mild tics) the long-term outcome seems to depend on: severity of initial episode, number of recurrences, family history and many other factors.

Again, the acute cases we are discussing here, like in any encephalitic reaction it takes time to heal and outcomes of each child are uncertain. But most parents agree, that by puberty, if children are protected by one of the PANDAS treatments (antibiotics at each exacerbation or IVIG or PEX if the child does not improve on antibiotics) —they have a healthy outcome and function without problems. The proper function of the basal ganglia is difficult to monitor. So doctors aren’t able yet to determine if any persistent symptoms are related to dysfunction (temporary) or damage (longer term).

Therefore, in acute PANDAS cases, where cessation of acute symptoms just does not occur parents opt for IVIG or Plasma exchange in order to prevent brain damage.

The landmark paper regarding the use of Plasma Exchange and IVIG, by Perlmutter, et al (1999) clearly shows that the 30 children involved very much improved after these procedures.

A 2007 Turkish  study, Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections,  follows four ADULTS receiving PEX treatment and cites, “In all 4 cases plasmapheresis treatment resulted in significant improvement in both obsessive-compulsive symptoms and tics.”

Despite this, there is criticism of these therapies. Of the 50+ doctors we have discussed this with they say it is because of a lack of “clear diagnostic guidelines for PANDAS.”

For families who have lived through the acute onset and sometimes debilitating continuance of PANDAS symptoms – the choice to try PEX or IVIG is clear. Our children are suffering greatly in these cases. Again, this is all anecdotal, non-scientific, information only.

The Current Group of PANDAS cases

Over 25% of the parents in our small group of 80 have found that antibiotics after several months, though successful at creating an initial cessation of symptoms, ultimately find their child’s autoimmune system so taxed (reacting to many other viral and bacterial infections) that they are seeking IVIG or PEX.

Most parents who have done IVIG in our group (approximately 13 with more families doing IVIG within the remaining months of 2009) say a 70-90% cessation of symptoms post-IVIG took 3- 4 months. A nearly 100% cessation occurs at the end of one year – with low level hyperactivity or anxiety appearing during times of fatigue. The IVIG procedure was done generally after 6 mos. to 1 year of sustained suffering from periodic acute PANDAS symptoms despite antibiotics.

Doctors we have talked to say the vast majority (approx. 200 children based on conversations) of PEX and IVIG patients have not had to repeat the procedures and assume families are satisfied that their children are recovered.

However, there are reports of the need to repeat IVIG and PEX for about 6 patients with acute onset of PANDAS. And that after those repeat treatments – the children improved greatly.

In 2011, a new NIMH IVIG study for PANDAS began recruitment.  Swedo “predict(s) that IVIG will have striking benefits for OCD and other psychiatric symptoms, and will prove most effective for children who show high levels of anti-brain antibodies when they enter the study”. (2012 press release).

It has been recommended by physicians that the PANDAS child remain on prophylactic antibiotics in accordance to the RF guidelines established by the American Academy of Pediatrics Journal. The guideline By the AAP is for 5 years after last attack or until age 21 (whichever is longer). According to the World Health Organization, the duration of prophylaxis for ARF is 5 years after last attack until 18 years old (whichever is longer). 

Children who have been ill with Sydenham Chorea, Rheumatic Fever or PANDAS have a risk of developing a more severe reaction if infected with strep again. Prophylaxis prevents re-infection.

Children are believed to be around strep at least 10 times per year – increasing their susceptibility to strep.

Long term prophylactic antibiotic use for PANDAS has been shown in the study Antibiotic Prophylaxis with Azithromycin or Penicillin for Childhood-Onset Neuropsychiatric Disorders to “…play a role in the management of children in the PANDAS subgroup, as well as provide support for the assertion that GAS plays an etiologic role in some children with tics and/or obsessive-compulsive Disorder”. In that same study, it also states that “There was a 61% overall reduction in neuropsychiatric symptom exacerbations during the year of antibiotic prophylaxis and a 94% reduction in GAS triggered neuropsychiatric symptom exacerbations.”

In the Current Group of PANDAS cases approx. 10% of the children recovered after several weeks or several months of symptoms. They remained on prophylactic antibiotics (up to 1 year) and had a complete cessation of symptoms and the parents have taken the children off antibiotics. If the child has a reoccurrence of symptoms they will begin antibiotics again. However, as explained above under “Will My Child Outgrow This?“, “Even if a subsequent exacerbation is caught quickly, it does not mean it will be an easier recovery or any less severe. We are hearing from anecdotal reports that often exacerbations worsen each time they occur.  There is no way in knowing how a child will react. The immune system is on high alert. No matter what your choice of treatment, protecting the child from more strep infections or proximity to ANYONE sick with strep in the First Year of Healing needs to remain high priority. We, as parents and doctors, owe it to these children to give them the best chance of recovery and no future suffering.”

The other approx. 15% are continuing on daily prophylactic antibiotics beyond 6 mos. as their children still have low level anxiety, mild ocd/tics, and hyperactivity and are deciding if their children’s condition is manageable or not.

Finally, there is the another 15% of the group that has gradually outgrown PANDAS at puberty and are now between 14-18 years old. They only remained on antibiotics throughout childhood with no IVIG or Plasma Exchange to lessen severity. Most of the parents have said their childhood was challenging and difficult on the family life. Their children had to be in special IEP classes in Grade School. Their doctors gave antibiotics periodically when strep was in the household or classroom environment or if they got a strep infection. They are not currently on prophylactic antibiotics post-puberty but are vigilant.

The NIMH’s stance on prophylactic antibiotics

According to the recently updated NIMH page (updated 2012), prophylactic antibiotics “may be helpful to use antibiotics as prophylaxis (prevention) against strep infections. Prophylactic antibiotics have proven to be quite beneficial to patients with rheumatic fever and Sydenham chorea”. The NIMH also provides a graph from the above mentioned Snider et al. study that shows improvements with Penicillin and Azithromycin in children with PANDAS. “The red line indicates the start of antibiotics prophylaxis, so marks to the left of the line represents the year prior to receiving antibiotics (most children were symptomatic for at least several months during the year) and the area to the right of the line shows the symptomatic months while taking penicillin or azithromycin.”

Following is data compiled based on parent emails. Please do not rely on this as scientific evidence of the benefits of any treatment. It is a picture of each child’s journey only.

Original 200 PANDAS Case Summaries (pdf)

Follow Up Survey Results – Treatment and Relapse (an update of the 200 PANDAS Case Summaries)
by Diana Pohlman (December 2012):

I recently reported at the UC Irvine Conference results of anecdotal, self-reports of 200 PANDAS cases followed from 2010-present.

In 2010, we reviewed 200 self-reported PANDAS cases (acute, sudden onset) to see if children recovered from PANDAS when treated. We found the vast majority greatly improved and had very minor, if any, remaining symptoms after one year of treatment. This is not scientifically reviewed but with the lack of scientific data available to us, we wanted to give families a message of hope.

Here are the results from 2010 :

ONE YEAR POST TREATMENT Average Age 4-10 yrs, Boys 2:1 Girls

• One or two IVIG’s:
  IVIG with Antibiotics = 88 children total
  Improved = 69
  Relapsed = 19
  12 relapses when “longterm” 2+ years untreated*

• Antibiotics Only:
  Antibiotics Only = 78 children total
  Improved = 63
  Relapsed = 15
  2 relapses when “longterm” 2+ years untreated

• Other:
  8 children did PEX exchange (2 with great success and other with moderate success*)
  2 remitted with no treatment
  24 did not respond to inquiries

*The majority of these children had complex cases: co-morbid autoimmune disease, PANDAS illness untreated beyond 4+ years, autism, or repeated streptococcus infections within first year of treatment.

Were there relapses after one year? 25% said yes, mildly: Between 2011-12, I followed up with approximately 80 of the above parents. I was not able to be as thorough with statistics as I returned to work when my own son healed. But for what it is worth – those that improved maintained a majority of improvement but approximately 25% reported “minor upticks” of symptoms (mild ocd, anxiety or tics). Only 2% of families reported major relapses and the reasons for the relapse are, sadly, unclear to me. Sometimes it may just be severity of the attack. This is why opinions from neurologists like Dr. Finn Somnier that acknowledge potential encephalopathy are important…..I think at times this can happen with PANDAS.

Parents said minor upticks tended to require an increase in antibiotics (increase from prophylactic to treatment dose) for 5 to 6 weeks, assistance with ibuprofen or prednisone for a few weeks and sometimes and H1 or H2 blocker as well. Each exacerbation lasted about one to two months but NEVER approached the initial onset level of PANDAS.

Parents said these mild upticks occurred sometimes (but not always) when the immune process was stressed: cold, flu, fever or cough; strep infection, loose teeth, once with severe food poisoning, and in a few instances, tonsils that were infected were removed. Two parents whose children had a substantial increase in OCD and fears, though not as severe as the initial onset, did IVIG one additional time and the children improved to the point that all OCD/fears were gone. Tics diminished but were not entirely absent.

Finally, these reports of improvement match what I hear the majority of the time from the majority of treating experts. There is no evidence that repeated monthly high dose IVIG’s are warranted in the majority of cases . However, complicated cases with immune deficiency, autoimmune disease, or autism often report that “one or two IVIG’s are not enough.”

No matter what, it takes 3 to 6 months to see a diminishment of symptoms post-IVIG or antibiotic treatment. I was able to watch evidence of the auto-antibodies and CamKinase II diminishment over 3 to 6 months together with behavioral improvement with Dr. Cunningham’s test.